The objectives of the proposed research (a new phase of a long-range program on the microchemical anatomy and pathology of mammalian cerebral cortex) are to survey the chemoarchitectonics of proteolytic enzymes in autopsy specimens of normal and pathological human prefrontal eulaminate isocortex (Brodmann area 9) by means of the principles and techniques of quantitative histochemistry (Linderstrom-Lang school). Selected exo- (7) and endopeptidases (5) will be assayed microchemically in microtome prepared samples so as (a) to identify the proteolytic capabilities of human cortex in relation to standard biochemical parameters (solids, protein, DNA) and to RNA concentration serving as index of protein synthetic potential, and (b) to establish the intracortical distribution pattern of each enzyme in relation to architectonic lamination. The results should be indicative of potentials for protein turnover in human isocortex and their distributions within its substituent architectonic layers, and should enable inferential correlations between proteinase and peptidase activities and aspects of histological structure. In so far as possible, following establishment of a normative data base, comparative observations of the foregoing types will be made on autopsy specimens of cortex from patients with mental disease both with and without identifiable histopathological changes (dementias, major psychoses, etc.).